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BU08028 Displays a Promising Therapeutic Profile as an Analgesic in Monkeys
Author(s) -
Ding Huiping,
Czoty Paul,
CamiKobeci Gerta,
Sukhtankar Devki,
Nader Michael,
Husbands Stephen,
Ko MeiChuan
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.616.2
Subject(s) - nop , nociceptin receptor , pharmacology , buprenorphine , analgesic , nociception , antagonist , agonist , chemistry , opioid , receptor antagonist , allodynia , hyperalgesia , receptor , medicine , opioid peptide
BU08028, a novel buprenorphine analog, displays similar receptor binding profile like buprenorphine but with improved binding affinity and efficacy on nociceptin/orphanin FQ peptide (NOP) receptors. The aim of this study was to characterize the pharmacological profile of BU08028 as an analgesic in rhesus monkeys. Systemic administration of BU08028 (0.001‐0.01 mg/kg) dose‐dependently produced antinociception against acute thermal nociception and capsaicin‐induced thermal allodynia. Compared to buprenorphine (0.01‐0.1 mg/kg), the antinociceptive effect of BU08028 was more potent and much longer‐lasting (i.e., more than 24 hours). BU08028‐induced antinociception was attenuated equally by both mu opioid (MOP) receptor antagonist naltrexone (0.03 mg/kg) and NOP antagonist J‐113397 (0.1 mg/kg), indicating that BU08028 is a bifunctional MOP/NOP agonist in primates. More importantly, BU08028 at antinociceptive doses did not compromise physiological functions including respiration and cardiovascular activities measured by the radio‐telemetric probes. Compared to MOP agonists, buprenorphine and remifentanil, BU08028 did not produce reinforcing effects in monkeys under the progressive‐ratio schedule of drug self‐administration. These findings demonstrate that BU08028 potently produced long‐lasting antinociception in the absence of common side effects associated with MOP agonists in primates. This study strongly supports the therapeutic potential of ligands with mixed MOP/NOP actions as innovative analgesics in humans (Supported by US‐PHS grants DA‐035359 and DA‐032568).